# A viral codon usage strategy enhances antigen production and protection in SFTSV mRNA vaccination

## TL;DR

This study shows that using a viral codon strategy in mRNA vaccines improves immune responses and protection against SFTSV at lower doses.

## Contribution

A novel HSVgB codon optimization strategy is introduced for low-dose, high-efficacy mRNA vaccines.

## Key findings

- HSVgB codon-optimized mRNA vaccines achieved higher antigen expression than human-optimized vaccines.
- The strategy induced stronger humoral and cellular immune responses and better protection at lower doses.
- It generated more bone marrow-resident antibody-secreting cells.

## Abstract

Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) is an emerging tick-borne pathogen with a high case-fatality rate and no approved vaccine, posing a global health threat. Human codon-optimized viral antigens can enhance mRNA vaccine efficacy by improving antigen expression but often requires high mRNA doses, increasing the risk of side effects. In this study, we introduce a codon optimization strategy using Herpes Simplex Virus 1 glycoprotein B (HSVgB) codon usage to develop an mRNA lipid nanoparticle (LNP) vaccine targeting the neutralizing Gn-H domain of SFTSV (sGn-H). The HSVgB codon-optimized mRNA vaccine [sGn-H (HSVgB)] achieved higher antigen expression and elicited stronger humoral and cellular immune responses than a human codon-optimized counterpart [sGn-H (human)]. Notably, sGn-H (HSVgB) induced more bone marrow-resident antibody-secreting cells and conferred superior protection against SFTSV at lower doses. These findings highlight HSVgB codon optimization may represent a promising strategy for enhancing the immunogenicity with low-dose mRNA immunization.